14th Grant

At the 95th Annual Meeting of the Japanese Biochemical Society, I gave an oral and poster presentation titled "Functional Analysis of STAT3 Acetylation in Carcinogenesis Induced by the Fusion Tyrosine Kinase NPM-ALK."

In anaplastic large cell lymphoma (ALCL), the fusion tyrosine kinase NPM-ALK is expressed due to chromosomal translocation. It has been reported that expressed NPM-ALK is constitutively activated and induces the phosphorylation of the transcription factor STAT3, thereby promoting cell proliferation and tumorigenesis. We newly discovered that in NPM-ALK-expressing Ba/F3 cells, the lysine residue at position 685 of STAT3 is acetylated in an NPM-ALK activity-dependent manner. In this study, we analyzed the physiological significance of STAT3 acetylation by reconstituting STAT3-knockdown NPM-ALK-expressing Ba/F3 cells with either wild-type STAT3 or an acetylation-inhibited STAT3 mutant (K685R). As a result, we revealed that STAT3 acetylation suppresses NPM-ALK-induced STAT3 phosphorylation and acts inhibitorily on cell proliferation and tumorigenesis induced by NPM-ALK.

Having the opportunity to present at the JBS meeting, I received feedback and questions from new perspectives from researchers in various fields, leading to discussions that will contribute to the future development of my research. Furthermore, exposure to presentations from other research areas and the latest research findings increased my motivation for research, making it a very valuable experience.

I am sincerely grateful for the generous support from Sato Pharmaceutical Co., Ltd., which made it possible for me to present at the conference. I intend to approach my research with even greater dedication in the future.

(Akira Mukai, 1st-year Master's student, Graduate School of Pharmaceutical Sciences)

I participated in the 95th Annual Meeting of the Japanese Biochemical Society held in Nagoya, Aichi, where I gave an oral and poster presentation on the theme "Analysis of the Molecular Mechanism of STAT5-Independent Cell Proliferation Induced by Erythropoietin."

Until now, the transcription factor STAT5 was considered necessary for the induction of red blood cell differentiation and proliferation by the hematopoietic cytokine erythropoietin (Epo). However, we found that Epo stimulation also induces cell proliferation in cells expressing a mutant Epo receptor (EpoR-HM) that does not induce STAT5 activation. Therefore, we performed gene expression analysis on EpoR-HM-expressing cells using a DNA microarray and revealed that Epo induces the expression of the proto-oncogene c-Myc in a STAT5-independent manner. We also clarified the molecular mechanism by which Epo induces c-Myc expression through the activation of the transcription factor STAT3 and the MEK-ERK pathway.

Through discussions with other researchers at this conference, I realized that future challenges include elucidating more detailed mechanisms and evaluating the impact on red blood cell differentiation. In particular, interacting with researchers of my own generation was a great source of motivation for my future research. I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support, which enabled my participation in this conference.

(Kengo Takeda, 1st-year, Doctoral Programs, Graduate School of Pharmaceutical Sciences)

I gave a poster and oral presentation on "Elucidation of the Role of STAT3 Phosphorylation in Carcinogenesis Induced by NPM-ALK" at the 95th Annual Meeting of the Japanese Biochemical Society held in Nagoya, Aichi.

In about half of patients with anaplastic large cell lymphoma, the fusion tyrosine kinase NPM-ALK is expressed due to the gene translocation t(2;5)(p23;35). NPM-ALK is constitutively activated and is known to induce carcinogenic signals via the transcription factor STAT3, but the detailed molecular mechanism remains unknown.

I investigated the physiological significance of the phosphorylation of STAT3 at Y705 and S727 in NPM-ALK-induced carcinogenesis by reconstituting NPM-ALK-expressing Ba/F3 cells in which STAT3 expression was suppressed using sh-RNA (STAT3-KD cells) with either wild-type STAT3 or phosphorylation-inhibited STAT3 mutants (Y705F, S727A). As a result, I revealed that NPM-ALK induces cell proliferation and tumorigenesis via the phosphorylation of STAT3 at Y705. Furthermore, I identified nine genes whose expression is induced by NPM-ALK via the phosphorylation of STAT3 at Y705. Through this research, I was able to clarify a part of the mechanism of carcinogenesis induced by NPM-ALK.

Through my presentation at the conference, I received many questions and opinions from numerous researchers, which were extremely helpful for advancing my research. Additionally, listening to the presentations of other researchers was a valuable experience that broadened my own knowledge.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for providing me with the opportunity to present at the conference through their research encouragement fund.

(Xin Lin, 3rd-year, Ph.D. program, Graduate School of Pharmaceutical Sciences)

At the 95th Annual Meeting of the Japanese Biochemical Society, I gave an oral and poster presentation titled "Analysis of the Molecular Mechanism of Neuroinflammation Suppression by Coffee." Epidemiological studies have shown that coffee consumption suppresses the onset and progression of neurodegenerative diseases such as Alzheimer's and Parkinson's, but the detailed mechanism is unknown. Therefore, this study focused on neuroinflammation, which is involved in the pathogenesis of these diseases, to examine the effects of coffee on neuroinflammation and to identify coffee components that suppress it. Through experiments using mouse microglial BV2 cells and a mouse model of neuroinflammation, we revealed that coffee has an activity that suppresses neuroinflammation. We also identified pyrocatechol, a component of coffee, as its active ingredient.

By presenting my research findings at the JBS meeting, I was able to receive numerous questions, advice, and suggestions from professors in various research fields. I was able to reconfirm the significance of this research from new perspectives and believe I have clarified the issues to be addressed in the future.

Finally, I would like to take this opportunity to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support in enabling my participation in the conference.

(Daisuke Murata, 2nd-year Master's student, Graduate School of Pharmaceutical Sciences)

I participated in the International Human Microbiome Consortium 2022, held in Kobe, Japan, and gave a poster presentation titled "γδT17 cells in Peyer's patches acquire the encephalitogenic phenotype through the activation by commensals."

This academic meeting brings together researchers conducting cutting-edge research on gut bacteriology and the human gut microbiome to share and discuss their findings. Because the gut microbiota affects a wide range of host physiological functions, including the immune, nervous, and metabolic systems, researchers from a broad spectrum of fields gathered. For me, as someone who usually conducts research in immunology, it was a great opportunity not only to expand my knowledge but also to engage in discussions with researchers from other fields.

During the conference, I had the opportunity to have a personal discussion with Noah Palm from Yale University, who studies the interaction between gut bacteria and the immune system. I was able to share my research findings and receive advice that will lead to further development.

This conference presentation was made possible by a research encouragement fund from Sato Pharmaceutical Co., Ltd. I would like to take this opportunity to express my gratitude.

(Seiga Komiyama, 1st-year, Ph.D. program, Graduate School of Pharmaceutical Sciences)

At the 51st Annual Meeting of the Japanese Society for Immunology, I gave an oral presentation titled "Development of the tolerogenic nanoparticle to induce antigen-specific regulatory T cells."

Many current treatments for allergic diseases are symptomatic therapies using pharmaceuticals, but symptoms recur if medication is discontinued. Allergen immunotherapy exists as a curative treatment for allergic diseases, but the pharmaceuticals used in this therapy still have challenges in terms of safety and efficiency.

This research aims to cure allergic diseases by re-educating the immune system, utilizing the environment of the intestinal tract, which is constantly exposed to various foreign substances like food antigens and gut bacteria and maintains immune tolerance to prevent unnecessary immune reactions and inflammation. To this end, we are conducting joint research with the Katayama Laboratory at Kyushu University to develop nanoparticles in which an antigen protein is cross-linked to mannan, a tolerogenic ligand for dendritic cells. At this conference, I presented an overview of the mechanism of action of these nanoparticles, experimental results to demonstrate it, and future challenges.

The section I was assigned to had many presentations closely related to basic research within molecular biology. Through the Q&A sessions and the presentations of other professors, I learned about ideas and research methods I was lacking, and I hope to apply this to the further development of my research. Finally, thanks to the support from Sato Pharmaceutical Co., Ltd., I was able to present at this conference. I would like to take this opportunity to express my gratitude.

(Hiroki Toriumi, 1st-year Master's student, Graduate School of Pharmaceutical Sciences)

I participated in The 9th Congress of the International Human Microbiome Consortium held in Kobe, Hyogo, and gave a poster presentation titled "Dietary factors facilitate the differentiation of follicular helper T cells in Peyer's patches."

Follicular helper T (Tfh) cells are abundant in Peyer's patches, the main lymphoid tissue of the small intestine, where they promote the germinal center reaction and stimulate IgA production. While gut bacteria are necessary for the induction of Tfh cell differentiation, the only known Tfh-inducing bacteria to date are segmented filamentous bacteria in mice, and no factors common to humans have been found. We have previously discovered that soybean flour in the diet induces the differentiation of Peyer's patch Tfh cells in mice. We have further clarified that this is dependent on gut bacteria and are currently working to identify the responsible bacteria that cause the Tfh cell-inducing effect of soybean flour.

At this conference, with the common thread of research involving gut and skin bacteria, I was able to interact with researchers from diverse backgrounds, not just immunology, and have meaningful exchanges of opinions, receiving advice from various perspectives. The symposium featured an impressive lineup of speakers, and it was fascinating to hear in detail about the latest research. I hope to leverage this experience to further advance my own research. This conference presentation was made possible by the research encouragement fund provided by Sato Pharmaceutical Co., Ltd. I would like to express my sincere gratitude.

(Kisara Muroi, 3rd-year, Doctoral Programs, Graduate School of Pharmaceutical Sciences)

I participated in the 17th International Conference on Bioactive Lipids held in New Orleans, USA, and gave a poster presentation titled "DHA-derived 19,20-EpDPE suppressed hepatic crown-like structure formation and the progression of liver fibrosis in mice." In my presentation, I reported on how DHA, an omega-3 fatty acid, is endogenously converted into active lipid metabolites in non-alcoholic steatohepatitis (NASH) and the molecular mechanism by which it exerts its disease progression-suppressing effect. My research focuses not only on the physiological functions of active lipids but also on which cells, which enzymes, and at what timing they are produced. When I presented that I had elucidated the above mechanism through a genetic approach using genetically modified mice lacking specific cells, enzymes, or receptors, there were people who continued to ask questions for over an hour after the presentation time ended, leading to a heated discussion in a very positive atmosphere at the conference. Furthermore, from these questions and discussions, I was able to understand the unique points and shortcomings of our research, as well as its current position in the global context. Additionally, there were many opportunities for diverse conversations with researchers from around the world, and it was very helpful to gain interesting insights for considering studying abroad in the future.

My participation and presentation at this conference were made possible by the research encouragement fund from Sato Pharmaceutical Co., Ltd. I would like to take this opportunity to express my gratitude.

(Hidenori Aoki, 4th-year, Doctoral Programs, Graduate School of Pharmaceutical Sciences)

I gave a poster presentation titled "Cyp4f18-deficient mice develop psoriasis-like dermatitis through dysregulated n-3 PUFA metabolism" at the 17th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases held in New Orleans, USA. This study demonstrates that the omega-3 fatty acid metabolic pathway in immune cells is important for maintaining skin homeostasis.

This conference brings together researchers from around the world who study bioactive lipids, providing an opportunity to engage with cutting-edge lipid research. I was able to listen to lectures by renowned researchers who have led lipid research, including a Nobel laureate, and also attend many presentations by young researchers who are currently leading the field, which was very inspiring.

A great number of people came to see my poster presentation. Although the discussions were in English, as it was my second international conference, I was able to engage in lively discussions without hesitation and expand my network among researchers. Additionally, through the poster presentations of other participants and subsequent interactions, I deepened my knowledge of lipid research broadly, making it a very meaningful time. I hope to apply the valuable experience gained at this conference to my remaining graduate school life and my research activities after graduation.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support for this conference presentation. I take this opportunity to thank them.

(Mio Yoshida, 3rd-year, Ph.D. program, Graduate School of Pharmaceutical Sciences)